Intramuscular injection of vaccine containing 50 mcg of type A cryptococcal capsular polysaccharide (glucuronoxylomannan, GXM) covalently linked to tetanus toxoid was well tolerated in more than 70 volunteers known to be seropositive for HIV-1. CD4 <200, 200-500 and >500/cu mm. A single booster dose of 50 mcg will be given at 6 months and antibody titers followed one year. Followup of 50 vaccinated normal volunteers found that the 25 receiving the 50 mcg dose had a better preservation of IgG anti-GXM titer at 6 month follow up, the titer having fallen from 76 units at two weeks to 31 units, compared to the 25 volunteers receiving 25 mcg, who had a fall from 48 to 15 units/ml. Forty nine of the 50 normal volunteers have been bled at one year following initial immunization to determine persistence of antibody. IgG purified from a vaccinated normal volunteer was injected into mice at a dose which induced anti-GXM levels comparable to those obtained in vaccinated normal volunteers. When injected intravenously with serotype A Cryptococcus neoformans, the mice were significantly protected against infection and death.